ABSTRACT. Objectives. To identify and study adults (21 years or older) who have a 46,XY karyotype and presented as infants or children with genital ambiguity, including a small phallus and perineoscrotal hypospadias, reared male or female.Methods. Participants were classified according to the cause underlying their intersex condition based on review of medical and surgical records. Long-term medical and surgical outcome was assessed with a written questionnaire and physical examination. Long-term psychosexual development was assessed with a written questionnaire and semistructured interview.Results. Thirty-nine (72%) of 54 eligible patients participated. The cause underlying genital ambiguity of participants included partial androgen insensitivity syndrome (n ‫؍‬ 14; 5 men and 9 women), partial gonadal dysgenesis (n ‫؍‬ 11; 7 men and 4 women), and other intersex conditions. Men had significantly more genital surgeries (mean: 5.8) than women (mean: 2.1), and physician-rated cosmetic appearance of the genitalia was significantly worse for men than for women. The majority of participants were satisfied with their body image, and men and women did not differ on this measure. Most men (90%) and women (83%) had sexual experience with a partner. Men and women did not differ in their satisfaction with their sexual function. The majority of participants were exclusively heterosexual, and men considered themselves to be masculine and women considered themselves to be feminine. Finally, 23% of participants (5 men and 4 women) were dissatisfied with their sex of rearing determined by their parents and physicians.Conclusions. Either male or female sex of rearing can lead to successful long-term outcome for the majority of cases of severe genital ambiguity in 46,XY individuals.We discuss factors that should be considered by parents and physicians when deciding on a sex of rearing for such infants. Pediatrics 2002;110(3). URL: http://www. pediatrics.org/cgi/content/full/110/3/e31; intersex, sex assignment, gender, androgen insensitivity, gonadal dysgenesis, psychosexual, genital reconstruction, hormone replacement.ABBREVIATIONS. PAIS, partial androgen insensitivity syndrome; PGD, partial gonadal dysgenesis. D uring fetal sex differentiation, genetic males who are unable to masculinize their sex ducts and external genitalia can be classified into 2 major etiologic groups: 1) the inability of the fetus to produce sufficient amounts of testosterone and dihydrotestosterone or 2) the inability of the fetus to respond to androgens that are present in normal amounts. 1 We previously described a population of 46,XY subjects who presented to the Pediatric Endocrinology Clinic of Johns Hopkins Hospital with varying degrees of undermasculinized genitalia. 2 In this population, the most difficult group to treat in terms of gender assignment is that of individuals who were born with ambiguous genitalia that includes a small phallus and perineoscrotal hypospadias. 3 For this group of patients, there is a lack of agreement about optimal sex ...

These cases highlight the importance of StAR-dependent steroidogenesis during fetal development and early infancy; expand the geographic distribution of this condition; and finally establish a new, prevalent StAR mutation (L260P) for the Swiss population.

Our study describes nine single nucleotide changes in the GCM2 gene that represent polymorphisms. Although GCM2 mutations appear to be an uncommon cause of IH, the wide variety of GCM2 polymorphisms suggests that variant alleles may have a role in determining parathyroid function.

Although the molecular basis of pseudohypoparathyroidism type 1b (PHP type 1b) remains unknown, a defect in imprinting at the GNAS1 locus has been suggested by the consistent finding of paternal-specific patterns of DNA methylation on maternally inherited GNAS1 alleles. To characterize the relationship between the genetic and epigenetic defects in PHP type 1b, we analyzed allelic expression and methylation of CpG islands within exon 1A of GNAS1 in patients with sporadic PHP type 1b and in affected and unaffected individuals from five multigenerational kindreds with PHP type 1b. All subjects with resistance to parathyroid hormone (PTH) showed loss of methylation of the exon 1A region on the maternal GNAS1 allele and/or biallelic expression of exon 1A-containing transcripts, consistent with an imprinting defect. Paternal transmission of the disease-associated haplotype was associated with normal patterns of GNAS1 methylation and PTH responsiveness. We found that affected and unaffected siblings in one kindred had inherited the same GNAS1 allele from their affected mother, evidence for dissociation between the genetic and epigenetic GNAS1 defects. The absence of the epigenetic defect in subjects who have inherited a defective maternal GNAS1 allele suggests that the genetic mutation may be incompletely penetrant, and it indicates that the epigenetic defect, not the genetic mutation, leads to renal resistance to PTH in PHP type 1b.